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Synthesis of Triazole Schiff's Base Derivatives and Their Inhibitory Kinetics on Tyrosinase Activity.

Yu F, Jia YL, Wang HF, Zheng J, Cui Y, Fang XY, Zhang LM, Chen QX - PLoS ONE (2015)

Bottom Line: The results together with the anti-tyrosinase activities data indicated that substitution on the second position of benzene ring showed superior ant-ityrosinase activities than that on third position, and that hydroxyl substitutes were better than fluorine substitutes.In addition, two benzene rings connecting to the triazole ring would produce larger steric hindrance, and affect the bonding between tyrosinase and inhibitors to decrease the inhibitory effects.The anti-tyrosinase effects of these compounds were in contrast to their antioxidant activities.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Cellular Stress Biology, Key Laboratory of the Ministry of Education for Coastal and Wetland Ecosystems, School of Life Sciences, Xiamen University, Xiamen, 361005, China.

ABSTRACT
In the present study, new Schiff's base derivatives: (Z)-4-amino-5-(2-(3- fluorobenzylidene)hydrazinyl)-4H-1,2,4-triazole-3-thiol (Y1), (Z)-3-((2-(4-amino-5- mercapto-4H-1,2,4-triazol-3-yl)hydrazono)methyl)phenol (Y2), (Z)-2-((2-(4-amino-5- mercapto-4H-1,2,4-triazol-3-yl)hydrazono)methyl)phenol (Y3) and 3-((Z)-(2-(4- (((E)-3-hydroxybenzylidene)amino)-5-mercapto-4H-1,2,4-triazol-3-yl)hydrazono)methyl)phenol (Y4) were synthesized and their structures were characterized by LC-MS, IR and 1H NMR. The inhibitory effects of these compounds on tyrosinase activites were evaluated. Compounds Y1, Y2 and Y3 showed potent inhibitory effects with respective IC50 value of 12.5, 7.0 and 1.5 μM on the diphenolase activities. Moreover, the inhibition mechanisms were determined to be reversible and mixed types. Interactions of the compounds with tyrosinase were further analyzed by fluorescence quenching, copper interaction, and molecular simulation assays. The results together with the anti-tyrosinase activities data indicated that substitution on the second position of benzene ring showed superior ant-ityrosinase activities than that on third position, and that hydroxyl substitutes were better than fluorine substitutes. In addition, two benzene rings connecting to the triazole ring would produce larger steric hindrance, and affect the bonding between tyrosinase and inhibitors to decrease the inhibitory effects. The anti-tyrosinase effects of these compounds were in contrast to their antioxidant activities. In summary, this research will contribute to the development and design of antityrosinase agents.

No MeSH data available.


Docking information of compound Y1 to Y4 in the bonding site of tyrosinase.(A) The molecular docking process of compound Y1. (I)The global figure of docking. (II)The enlarged figure of docking center. The inhibitor molecule was shown as yellow, while the copper ion was in green. (III, B, C, D) the interaction between compound Y1 to Y4 and the residues of tyrosinase, respectively.
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pone.0138578.g007: Docking information of compound Y1 to Y4 in the bonding site of tyrosinase.(A) The molecular docking process of compound Y1. (I)The global figure of docking. (II)The enlarged figure of docking center. The inhibitor molecule was shown as yellow, while the copper ion was in green. (III, B, C, D) the interaction between compound Y1 to Y4 and the residues of tyrosinase, respectively.

Mentions: Molecular simulations further clarified the underlying mechanisms of compounds in the active center, which would give a more convincing conclusion by combining the results of copper ions mutual effect. Fig 7 depicted the docking conformation of the four compounds in the tyrosinase catalytic center.


Synthesis of Triazole Schiff's Base Derivatives and Their Inhibitory Kinetics on Tyrosinase Activity.

Yu F, Jia YL, Wang HF, Zheng J, Cui Y, Fang XY, Zhang LM, Chen QX - PLoS ONE (2015)

Docking information of compound Y1 to Y4 in the bonding site of tyrosinase.(A) The molecular docking process of compound Y1. (I)The global figure of docking. (II)The enlarged figure of docking center. The inhibitor molecule was shown as yellow, while the copper ion was in green. (III, B, C, D) the interaction between compound Y1 to Y4 and the residues of tyrosinase, respectively.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4589318&req=5

pone.0138578.g007: Docking information of compound Y1 to Y4 in the bonding site of tyrosinase.(A) The molecular docking process of compound Y1. (I)The global figure of docking. (II)The enlarged figure of docking center. The inhibitor molecule was shown as yellow, while the copper ion was in green. (III, B, C, D) the interaction between compound Y1 to Y4 and the residues of tyrosinase, respectively.
Mentions: Molecular simulations further clarified the underlying mechanisms of compounds in the active center, which would give a more convincing conclusion by combining the results of copper ions mutual effect. Fig 7 depicted the docking conformation of the four compounds in the tyrosinase catalytic center.

Bottom Line: The results together with the anti-tyrosinase activities data indicated that substitution on the second position of benzene ring showed superior ant-ityrosinase activities than that on third position, and that hydroxyl substitutes were better than fluorine substitutes.In addition, two benzene rings connecting to the triazole ring would produce larger steric hindrance, and affect the bonding between tyrosinase and inhibitors to decrease the inhibitory effects.The anti-tyrosinase effects of these compounds were in contrast to their antioxidant activities.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Cellular Stress Biology, Key Laboratory of the Ministry of Education for Coastal and Wetland Ecosystems, School of Life Sciences, Xiamen University, Xiamen, 361005, China.

ABSTRACT
In the present study, new Schiff's base derivatives: (Z)-4-amino-5-(2-(3- fluorobenzylidene)hydrazinyl)-4H-1,2,4-triazole-3-thiol (Y1), (Z)-3-((2-(4-amino-5- mercapto-4H-1,2,4-triazol-3-yl)hydrazono)methyl)phenol (Y2), (Z)-2-((2-(4-amino-5- mercapto-4H-1,2,4-triazol-3-yl)hydrazono)methyl)phenol (Y3) and 3-((Z)-(2-(4- (((E)-3-hydroxybenzylidene)amino)-5-mercapto-4H-1,2,4-triazol-3-yl)hydrazono)methyl)phenol (Y4) were synthesized and their structures were characterized by LC-MS, IR and 1H NMR. The inhibitory effects of these compounds on tyrosinase activites were evaluated. Compounds Y1, Y2 and Y3 showed potent inhibitory effects with respective IC50 value of 12.5, 7.0 and 1.5 μM on the diphenolase activities. Moreover, the inhibition mechanisms were determined to be reversible and mixed types. Interactions of the compounds with tyrosinase were further analyzed by fluorescence quenching, copper interaction, and molecular simulation assays. The results together with the anti-tyrosinase activities data indicated that substitution on the second position of benzene ring showed superior ant-ityrosinase activities than that on third position, and that hydroxyl substitutes were better than fluorine substitutes. In addition, two benzene rings connecting to the triazole ring would produce larger steric hindrance, and affect the bonding between tyrosinase and inhibitors to decrease the inhibitory effects. The anti-tyrosinase effects of these compounds were in contrast to their antioxidant activities. In summary, this research will contribute to the development and design of antityrosinase agents.

No MeSH data available.